title: Functional impairment in submandibular gland of rats induced by 5-fluorouracil and calcium leucovorin.
abstract: One of the main clinical problems during chemotherapy is the occurrence of severe systemic toxicities, including those related to the stomatognathic system, which contribute to reducing the patient's quality of life. The most frequent oral complications are mucositis, dysgeusia, inflammation, gingival bleeding and decreased salivary flow or hyposalivation, a factor that predisposes to xerostomia, and other local complications that alter the homeostasis of the system. The purpose of this study was to evaluate the functional activity of salivary glands in Wistar rats subject to chemotherapy by measuring salivary flow, glycogen levels and glandular tissue response to autonomic nervous system agonists. Five experimental groups were used: 1) Control group fed "ad libitum"; 2) 5-fluorouracil (20 mg/kg body weight); 3) Calcium leucovorin (10 mg/kg body weight); 4) 5-fluorouracil + calcium leucovorin (20 and 10 mg/kg, respectively) by intraperitoneal injection for five consecutive days and 5) control with paired diet. Groups 1 and 5 did not receive drugs. Treatment with fluorouracil + leucovorin produced an increase in stimulated salivary flow and a higher response to increasing doses of beta agonists compared to other experimental groups. In both groups treated with cytostatic drugs, blocking of glycogen consumption at the end of the experimental period was observed. Our work suggests that salivary secretion may be affected by a dual mechanism: the first would be toxicity induced by 5-FU, which would cause depression of the process of glucose utilization. The second mechanism would affect the sympathetic autonomic reflex arc. In this instance, the synergistic action of 5-FU + LV would have a negative effect on the nerve activity with a reduction of salivary secretion. This would explain the hyposalivation, cited by several authors in patients undergoing the 5-FU + LV scheme in the treatment of colon carcinoma.
authors.affiliation: Department of Physiology, School of Dentistry, National University of Córdoba, Argentina. marceloadrianmazzeo@yahoo.com.ar
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Mazzeo
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Linares
authors.forename: María M
authors.initials: MM
authors.lastname: López
authors.forename: Raquel V
authors.initials: RV
authors.lastname: Gallará
authors.forename: Evelin
authors.initials: E
authors.lastname: Bachmeier
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Wietz
authors.forename: Ana B
authors.initials: AB
authors.lastname: Finkelberg
mesh_terms: D000818:Animals; D054697:Cytostatic Agents / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D002955:Leucovorin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000187:drug effects* / Q000503:physiopathology*
chemical_list: D054697:Cytostatic Agents; D002955:Leucovorin; D005472:Fluorouracil